ArticleCancer cell international2023
The 4-1BBζ costimulatory domain in chimeric antigen receptors enhances CD8+ T-cell functionality following T-cell receptor stimulation.
Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Phosphotyrosine proteomics reveals novel Zap70 and Itk pathway targets downstream of TCR and CAR in Jurkat T cells.Scientific reports · 2026Article
- FcεRγI promotes canine CD8 chimeric antigen receptor T cell cytotoxicity through a Syk-NF-κB axis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- CD147 regulates CD8iScience · 2026Article
- CAR-T cell therapy for glioblastoma: advances, challenges, and future directions.Annals of medicine and surgery (2012) · 2025Review
- Protocol for the simultaneous activation and lentiviral transduction of primary human T cells with artificial T cell receptors.STAR protocols · 2025Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundChimeric antigen receptor (CAR) T-cells have revolutionized the treatment of CD19- and B-cell maturation antigen-positive haematological malignancies. However, the effect of a CAR construct on the function of T-cells stimulated via their endogenous T-cell receptors (TCRs) has yet to be comprehensively investigated.
methodsExperiments were performed to systematically assess TCR signalling and function in CAR T-cells using anti-mesothelin human CAR T-cells as a model system. CAR T-cells expressing the CD28 or 4-1BB costimulatory endodomains were manufactured and compared to both untransduced T-cells and CAR T-cells with a non-functional endodomain. These cell products were treated with staphylococcal enterotoxin B to stimulate the TCR, and in vitro functional assays were performed by flow cytometry.
resultsIncreased proliferation, CD69 expression and IFNγ production were identified in CD8+ 4-1BBζ CAR T-cells compared to control untransduced CD8+ T-cells. These functional differences were associated with higher levels of phosphorylated ZAP70 after stimulation. In addition, these functional differences were associated with a differing immunophenotype, with a more than two-fold increase in central memory cells in CD8+ 4-1BBζ CAR T-cell products.
conclusionOur data indicate that the 4-1BBζ CAR enhances CD8+ TCR-mediated function. This could be beneficial if the TCR targets epitopes on malignant tissues or infectious agents, but detrimental if the TCR targets autoantigens.
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